a study of duvelisib in combination with rituximab and bendamustine vs placebo in combination with rituximab and bendamustine in subjects with previously-treated indolent non-hodgkin lymphoma (bravura)

Conditions: Indolent Non-Hodgkin's Lymphoma; Follicular Lymphoma; Small Lymphocytic Lymphoma; Marginal Zone Lymphoma

Summary: this study will evaluate the efficacy and safety of duvelisib in combination with bendamustine and rituximab (dbr) vs placebo in combination with bendamustine and rituximab (pbr) in subjects with previously-treated indolent non-hodgkin lymphoma (inhl).

study ipi-145-22 is an international, multicenter, randomized, double-blind, placebo-controlled, two-arm phase 3 study designed to evaluate efficacy and safety of dbr vs pbr in subjects with previously-treated inhl (including follicular lymphoma \[fl\], small lymphocytic lymphoma \[sll\] and marginal zone lymphoma \[mzl\]). approximately 600 subjects will receive 25 mg of duvelisib or placebo, orally bid for 28 day continuous cycles, in combination with 375 mg/m2 of rituximab given on day 1 of cycles 1-6 and 90 mg/m2 of bendamustine given on day 1 and day 2 of cycles 1-6. subjects will receive duvelisib until disease progression or unacceptable toxicity.

Eligibility criteria:
inclusion criteria: * diagnosis of inhl with one of the following histologic sub-types and grade: * follicular lymphoma (fl)grade 1, 2, or 3a * small lymphocytic lymphoma (sll) * marginal zone lymphoma (mzl)( splenic, nodal, or extranodal) * have received the following systemic treatments for inhl: * an anti-cd20 antibody; and * chemotherapy * at least 1 measurable disease lesion \> 1.5 cm in at least one dimension by computed tomography (ct)/ct-pet or magnetic resonance imaging (mri) * eastern cooperative oncology group (ecog) performance status 0 to 2 (corresponds to karnofsky performance status \[(kps) ≥60%\]) exclusion criteria: * clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3b fl * refractory to bendamustine + rituximab therapy or single-agent bendamustine 120 mg/m2, with refractory defined as: - progression of disease while receiving or within 6 months of completing treatment * severe allergic or anaphylactic reaction to any monoclonal antibody therapy, murine protein, or known hypersensitivity to any of the study drugs * received prior allogeneic transplant * received prior treatment with a phosphoinositide-3-kinase (pi3k) inhibitor * infection with hepatitis b, hepatitis c, or human immunodeficiency virus (hiv). * history of tuberculosis treatment within the two years prior to randomization * history of chronic liver disease, veno-occlusive disease, or alcohol abuse * ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids \> 20 mg of prednisone (or equivalent) daily (qd) * ongoing treatment for systemic bacterial, fungal, or viral infection at screening * unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (hsv), or herpes zoster (vzv) at screening * concurrent active malignancy other than adequately treated non-melanoma skin cancer or lentigo maligna without evidence of invasive disease or adequately treated cervical carcinoma in situ without evidence of disease * history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or a pacemaker within the last 6 months prior to screening * history of progressive multifocal leukoencephalopathy

Keywords: phase 3 inhl follicular lymphoma fl pi3k small lymphocytic lymphoma sll marginal zone lymphoma mzl